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Few studies have specifically evaluated controller therapy in patients with mild persistent asthma. We used a subgroup analysis to investigate the effects of montelukast, a potent cysteinyl leukotriene receptor antagonist, on adult patients on the milder end of the asthma severity spectrum. We have identified seven double-blind, randomized, placebo-controlled studies of adult patients with mild-to-moderate chronic asthma in which montelukast was investigated. Subsets of patients with baseline forced expiratory volume in 1 sec (FEV₁) >80% and >75% predicted or further restricted by less than daily rescue β -agonist use were included as four cohorts (A, B, C, D), and efficacy measures, including change in FEV₁rescue-free days, β -agonist use, nocturnal awakenings and blood eosinophil counts were evaluated. Cohorts A to D comprised 21%, 8%, 11%, and 4%, respectively, of patients from these studies. Mean pretreatment FEV₁ranged from 81% to 84% predicted and daily β -agonist use from 2·4 to 4·5 puffs day⁻¹in the four cohorts. Pooled results demonstrated a treatment effect for montelukast over placebo in all cohorts, for all endpoints. There was a significant improvement in FEV₁in montelukast-treated patients (7–8% over baseline) compared with placebo (1–4% over baseline, between-group difference P≤0·02) for all cohorts. Similarly, the percentage of rescue-free days increased substantially more with montelukast (22–30%) than with placebo (8–13%). This subgroup analysis indicates that montelukast produced improvements in parameters of asthma control in patients with milder persistent asthma that should be confirmed in additional prospective trials. Copyright 2001 HARCOURT PUBLISHERS LTD.

Abstract BackgroundMontelukast, a leukotriene receptor antagonist, improves parameters of asthma control including forced expiratory volume in one second (FEV₁) when given orally to patients aged six years or older. This study was undertaken to compare the effect on FEV₁ of intravenous and oral montelukast and placebo during the 24 hour period following administration. Methods Fifty one asthmatic patients (FEV₁ 40–80% predicted and ≥15% improvement after inhaled β agonist) were enrolled in a double blind, single dose, three period, crossover study to receive intravenous montelukast (7 mg), oral montelukast (10 mg), or placebo in a randomised fashion. The primary end point was area under the curve (AUC)_{0–24 h} of the percentage change from baseline in FEV₁. Additional end points were maximum percentage change in FEV₁ and percentage change at different time points. Results Compared with placebo, intravenous and oral montelukast significantly increased the AUC_{0–24 h} (means of 20.70%, 15.72%, and 7.75% for intravenous, oral and placebo, respectively; no statistical difference between intravenous and oral). The difference in least square means from placebo for intravenous montelukast was 13.27% (95% CI 7.07 to 19.46), p<0.001 and for oral montelukast was 7.44% (95% CI 1.20 to 13.68), p = 0.020. The maximum percentage change in FEV₁ was not significantly different for intravenous and oral montelukast (difference in least square means 6.78% (95% CI –0.59 to 14.15), p = 0.071). The mean percentage change in FEV₁ for intravenous montelukast was greater than for oral montelukast within the first hour (15.02% vs 4.67% at 15 min, p≤0.001; 18.43% vs 12.90% at one hour, p<0.001 for intravenous and oral montelukast, respectively (placebo 3.05% at 15 minutes, 7.33% at one hour). Intravenous and oral montelukast were similar to placebo in the frequency of adverse events. Conclusions The onset of action for intravenous montelukast was faster than for oral montelukast and the improvement in airway function lasted over the 24 hour observation period for both treatments. Although not well understood, there was a trend toward a greater improvement in FEV₁ with intravenous than with oral montelukast. These findings suggest that leukotriene receptor antagonists should be investigated as a treatment for acute severe asthma.

OBJECTIVE: To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. DESIGN: Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. SETTING: 23 academic asthma centres in United States, Canada, and Europe. PARTICIPANTS: 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). INTERVENTIONS: Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. MAIN OUTCOME MEASURES: Last tolerated dose of inhaled corticosteroids. RESULTS: Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue. CONCLUSIONS: Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.

• The ability of six different operational definitions of schizophrenia to identify prospectively patients whose eventual prognosis would be poor was studied using data from a six-year follow-up of a series of 134 patients with functional psychoses. All six definitions were more successful at predicting a poor symptomatic outcome than a poor social outcome. Spitzer's Research Diagnostic Criteria, Carpenter's flexible criteria, and Langfeldt's criteria predicted a poor outcome as well as the original clinical diagnoses and were considerably better than the New Haven criteria, Schneider's first rank symptoms, or the computer program Catego.

En este estudio se expone un ensayo controlado de intervención social en familias de pacientes esquizofrénicos con alto riesgo de recaída. Los pacientes se seleccionaron por tener mucho contacto con familiares con alta emoción expresada. Todos los pacientes mantuvieron su tratamiento con medicamentos neurolépticos. Una mitad de las veinticuatro familias se asignaron al azar a cuidados rutinarios de pacientes externos, mientras que la otra mitad recibió un paquete de intervenciones sociales. Éste comprendía un programa de educación acerca de la esquizofrenia, un grupo para los parientes y sesiones familiares para parientes y pacientes. La tasa de recaída en el grupo de control fue de cincuenta por ciento comparada con el nueve por ciento del grupo experimental (P = 0.04). Los objetivos establecidos en las intervenciones terapéuticas se alcanzaron en el setenta y tres por ciento de las familias experimentales, en las cuales no hubo pacientes con recaídas. Los resultados evidencian el papel causal de la emoción expresada de los familiares en la recaída de pacientes esquizofrénicos, así como de la efectividad terapéutica de la intervención social combinada con el tratamiento farmacológico.

Este estudio es una replicación y extensión de un trabajo anterior llevado a cabo por Brown, Birley y Wing (1972) acerca de la influencia de la vida familiar en el curso de la esquizofrenia. Los principales resultados de Brown et al.han sido replicados en dos grupos clínicamente diferentes de pacientes psiquiátricos. La emoción expresada del familiar parece de nuevo estar asociada con la recaída independientemente de todos los otros factores sociales y clínicos investigados. Un nivel elevado de emoción expresada de los familiares, en el momento del ingreso del paciente, sigue siendo el mejor predictor aislado de recaída sintomática durante los nueve meses siguientes al alta. Además se han revelado efectos aditivos importantes entre varias influencias sociales y tratamientos farmacológicos, lo que hace posible predecir patrones de recaída en la esquizofrenia con considerable precisión. Los patrones de estas relaciones con la recaída son diferentes para los dos grupos clínicos estudiados: pacientes con psicosis esquizofrénica y con neurosis depresiva.

Standard laboratory yeast strains can be enriched for thymidine 5'-monophosphate (TMP) uptake derivatives that generate only a low percentage of respiratory-deficient colonies (petites) under inhibition of TMP biosynthesis. Such mutants incorporated bromodeoxyuridine 5'-monophosphate (BrdUMP) into both nuclear and mitochondrial deoxyribonucleic acid (mtDNA); however, they showed a selectivity for TMP over BrdUMP incorporation. The preferential incorporation of [3H]TMP or BrdUMP into mtDNA was strain dependent. The density increments after growth in the presence of BrdUMP reached 50 mg/ml for nuclear DNA and 22 mg/ml for mtDNA in CsCl gradients. Density shifts corresponding to 4% bromouracil substitution were easily detected. Preliminary density transfer experiments confirm that mtDNA does not replicate in synchrony with nuclear DNA.

The DNA of several strains of Saccharomyces cerevisiae was labeled by growing the culture in medium supplemented with thymidylate and bromodeoxyuridylate. It was thus possible to follow the course of mitochondrial DNA replication in density shift experiments by determining the buoyant density distribution of unreplicated and replicated DNAs in analytical CsCl gradients. DNA replication was followed for three generations after transfer of cultures from light medium to heavy medium and heavy medium to light medium. Under both conditions, the density shifts observed for mitochondrial DNA were those expected for semiconservative, nondispersive replication. This was further confirmed by analysis of the buoyant density of alkali-denatured hybrid mitochondrial DNA. With this method, no significant recombination between replicated and unreplicated DNA was detected after three generations of growth.